This Fogarty International Research Collaboration Award (FIRCA) proposal has been designed to expand and enhance the parent grant entitled "Hemorheology Studies Related to In Vivo Blood Flow," (HL 15722, H.J. Meiselman, PI), and to enhance, expand and increase the research capacity of the foreign scientist (Dr. Oguz K. Baskurt) and the foreign institution (Akdeniz University, Antalya, Turkey). The parent grant is focussed on the in vitro hemorheological behavior and RBC aggregation mechanisms of normal and pathologic human blood, whereas both Dr. Baskurt's expertise and this FIRCA proposal deal with the use of animal blood and in vivo blood flow studies. This proposal and the parent grant thus share common long-range goals related to the physiological correlates of altered RBC aggregation, yet employ complementary methodologies to achieve these objectives. The specific aims of this FIRCA proposal are: 1) to evaluate the effects of altered RBC aggregation on in vivo flow resistance, via the use of an in situ guinea pig hind limb system and an isolated rat heart preparation, in order to test the hypothesis that there is an optimal level of RBC aggregation which minimizes overall resistance to blood flow; 2) to determine the effects of altered RBC aggregation on rat heart trans-mural myocardial hematocrit distribution to test the hypothesis that there is an optimal level of RBC aggregation which preserves the normal physiological gradient; 3) to evaluate the effects of plasma viscosity on in vivo flow resistance in order to test the hypothesis that increased plasma viscosity modulates the influence of enhanced RBC aggregation. Note that an unique and important aspect of the proposed studies is the use of the PI's recently developed technique for modifying RBC aggregation via covalent binding of polymers to the RBC surface; this new method does not require foreign polymers or proteins to be added to native plasma and thus allows RBC aggregation and medium viscosity to be varied independently. Successful completion of the major aims of this program will provide quantitative information relevant to the effects of both enhanced and decreased RBC aggregation on vascular resistance and hematocrit distribution, and should offer therapeutic insight into clinical states associated with abnormal red cell aggregation.